Gag-specific CD4 T-cell proliferation, plasmacytoid dendritic cells and ethnicityin perinatally HIV-1-infected youths – The ANRS-EP38-IMMIP Study Short title: T-cell proliferation and dendritic cells

Abstract : In perinatally HIV-1-infected youths living in France, we previously reported that Gag-specific CD4 and CD8 T-cell proliferation is more frequently detected in patients of black ethnicity than in those of other ethnicities. We observed that black patients had higher levels of dendritic cells than other patients. We aimed to study the association of dendritic cell levels with Gag-specific T-cell proliferation. The ANRS-EP38-IMMIP study is an observational study of youths aged between 15 and 24 years who were perinatally infected with HIV. A single blood sample was drawn for virological and immunological assays. Data from cART treated 53 youths with undetectable plasma HIV RNA were analyzed. Gag-specific T-cell proliferation was assessed using a CFSE-based test. Peripheral blood myeloid and plasmacytoid dendritic cells (mDCs and pDCs) were phenotyped by flow cytometry. Plasma markers were quantified by ELISA or multiplex assays. Logistic regression was used for univariate and multivariate analyses. Patients with Gag-specific CD4 T-cell proliferative responses had significantly higher percentages and absolute counts of mDCs and pDCs in the peripheral blood than nonresponding patients. Gag-specific CD4 and CD8 T-cell proliferation were associated with lower plasma sCD14 levels. Plasma levels of IFN-α, TRAIL and chemokines involved in T-cell migration to secondary lymphoid organs were not associated with T-cell proliferation. Multivariate analysis confirmed the association between Gag-specific CD4 T-cell proliferation and pDC levels. In conclusion, dendritic cell levels are a robust correlate of the presence of Gag-specific T-cell proliferation in successfully treated youths.